Sleckman B P, Bardon C G, Ferrini R, Davidson L, Alt F W
Children's Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Immunity. 1997 Oct;7(4):505-15. doi: 10.1016/s1074-7613(00)80372-6.
We have used gene targeted mutational approaches to assess the role of the T cell receptor alpha (TCR alpha) enhancer (E alpha) in the control of TCR alpha and TCR delta gene rearrangement and expression. We show that E alpha functions in cis to promote V alpha to J alpha rearrangement across the entire J alpha locus, a distance of greater than 70 kb. We also show that E alpha is required for normal alphabeta T cell development; in this lineage, E alpha is required for germline J alpha expression, for normal expression levels of rearranged V alpha J alpha genes, and for expression of a diverse V alpha repertoire. In gamma delta T cells, E alpha is not required for VdeltaDJdelta rearrangement, but, surprisingly, is required for normal expression levels of mature VdeltaDJdelta transcripts and for expression of germline J alpha transcripts. Our findings imply that E alpha function is not limited to the TCR alpha components of the TCRalpha/delta locus or to the alpha beta lineage; rather, E alpha function is important in both alphabeta and gammadelta lineage T cells.
我们已采用基因靶向突变方法来评估T细胞受体α（TCRα）增强子（Eα）在控制TCRα和TCRδ基因重排及表达中的作用。我们发现Eα以顺式作用促进Vα至Jα在整个Jα基因座上的重排，该基因座跨度超过70 kb。我们还表明Eα是正常αβ T细胞发育所必需的；在该谱系中，Eα对于种系Jα的表达、重排后的VαJα基因的正常表达水平以及多样的Vα库的表达都是必需的。在γδ T细胞中，Eα对于VδDJδ重排不是必需的，但令人惊讶的是，它对于成熟VδDJδ转录本的正常表达水平以及种系Jα转录本的表达是必需的。我们的研究结果表明，Eα的功能不仅限于TCRα/δ基因座的TCRα组分或αβ谱系；相反，Eα的功能在αβ和γδ谱系T细胞中都很重要。
